Abstract Acute on chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS®) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. 189 patients with ACLF were randomized either to MARS® (n=95) or to standard therapy (SMT) (n=94). Ten patients (5 per group) were excluded due to protocol violations. In addition, 23 patients (MARS®: 19; SMT: 4) were excluded from per-protocol (PP) analysis (PP population n=156). Up to ten 6-8 hours MARS® sessions were scheduled. Main endpoint was 28-day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with MELD score over 20 points and with SBP as precipitating event was almost significantly greater in the MARS® group. 28-day survival was similar in the two groups in ITT and PP population (60. 7% vs.58.9 %; 60 % vs. 59.2 % respectively). After adjusting by confounders, a significant beneficial effect of MARS® on survival was not observed (OR: 0.87 CI 95 % 0.44-1.72). MELD score and HE at admission and the increase in serum bilirubin at day 4 were independent predictors of death. At day 4, a greater decrease in serum creatinine (p= 0.02) and bilirubin (p=0.001) and a more frequent improvement in HE (from grade II-IV to grade 0-I; 62.5 % vs. 38.2 %; p=0.07) was observed in MARS® group. Severe adverse events were similar. Conclusion: At scheduled doses, a beneficial effect on survival of MARS® therapy in patients with ACLF could not be demonstrated. However MARS® has an acceptable safety profile, has significant dialysis effect and non-significantly improves severe HE. (HEPATOLOGY 2012.).